Effect of oral faecal microbiota transplantation intervention for children with autism spectrum disorder: A randomised, double‐blind, placebo‐controlled trial

We conducted a randomised, double-blind, placebo-controlled trial of an oral faecal microbiota transplantation (FMT) intervention in children with autism spectrum disorder (ASD), and observed that there were differences in pre-and post-FMT intervention changes in the social domain scores of the Vineland Adaptive Behaviour Scale, third version (Vineland-3), with no severe adverse events (AEs) related to FMT occurring.


Effect of oral faecal microbiota transplantation intervention for children with autism spectrum disorder: A randomised, double-blind, placebo-controlled trial
To the Editor: We conducted a randomised, double-blind, placebocontrolled trial of an oral faecal microbiota transplantation (FMT) intervention in children with autism spectrum disorder (ASD), and observed that there were differences in pre-and post-FMT intervention changes in the social domain scores of the Vineland Adaptive Behaviour Scale, third version (Vineland-3), with no severe adverse events (AEs) related to FMT occurring.
Multiple studies have documented variations in the gut microbiota (GM) between children with ASD and typically developing children. 1,2Furthermore, specific gut microbes may modulate ASD-related behaviour through their metabolites. 1However, another study proposed that the GM is not the central driver of ASD symptoms; rather, the presence of restricted interests associated with ASD and a more limited dietary variety have been linked to reduced diversity in the GM. 3 The relationship between the GM and ASD remains enigmatic and complex as the age-old philosophical conundrum that has long been debated: which came first, the chicken or the egg?Some open-label studies 4-6 have demonstrated that FMT improved the core symptoms of patients with ASD, though these studies lacked comparable control groups, which may lead to disregard of potential placebo effects on efficacy evaluation.Therefore, we conducted this study.
A total of 103 eligible participants (Figure 1) were enrolled and randomised to receive either FMT or a placebo.These agents were administered during two 6day periods in the hospital, the first occurring in the initial week and the second in the fifth week of the study.Patients were not hospitalised during the interval between treatments.FMT capsules from five healthy donors were randomly provided to 8, 8, 11, 7 and 18 patients, respectively, with each patient receiving capsules from the same donor throughout the treatment process.The Social Responsiveness Scale, Second Edition (SRS-2), Vineland-3, and Autism Behaviour Checklist (ABC) scales were administered to measure outcomes before the start of the treatment as well as at Weeks 9 and 17 of the experiment for repeated measures (see Appendix S1).
The primary outcome was the difference in the change in the SRS-2 T-score between groups from baseline to Week 9 or Week 17, analysed using a mixed model for repeated measures.The secondary outcomes included Vineland-3 and ABC scores.Sensitivity analysis was conducted by comparing the changes in the scores of these scales between the FMT group with a donor gut microbiota colonisation rate of ≥20% or less than 20% and the placebo group.AEs were assessed (see Appendix S1).
No notable between-group differences were detected between the FMT (n = 52) and placebo (n = 51) groups in terms of demographic and baseline characteristics or scales (Appendix S1; Tables S1 and S2).
For the primary outcome, there were no significant differences in the SRS-2 T-scores between the two groups at baseline, Week 9 or Week 17 (Appendix S1; Figure S2).In the FMT group, the SRS-2 T-score decreased significantly from 78.33 at baseline to 74.59 at Week 17 (p = .03;Appendix S1; Table S3).From baseline to Week 17, significant reductions were observed in the T-scores of SRS-2 and its domains in both groups; however, the between-group differences in the changes in T-scores were not statistically significant (Table 1).
Regarding the secondary outcome, there were no significant differences in the ABC scores between the two groups at baseline, Week 9 or Week 17 (Appendix S1; Figure S4).The scores for both the FMT and placebo groups showed a reduction from baseline to Weeks 9 and 17 (Appendix S1; Table S3); however, there were no significant betweengroup differences (Table 1).Regarding Vineland-3 scores TA B L E 1 Changes in scores in the FMT and placebo groups from baseline to Week 9 and Week 17.   as a secondary outcome, there were no significant differences in the scores between the two groups at baseline, Week 9 or Week 17 (Appendix S1; Figure S3).After 17 weeks of treatment, the mean improvement in Vineland-3 symptoms was reported in both the FMT and placebo groups (Appendix S1; Table S3).Notably, a statistically significant disparity was observed in the alteration of socialisation domain score from baseline to Week 17 between the FMT and the placebo groups (difference = 5.05, 95% confidence interval [CI]: .31-9.79;Table 1).Additionally, compared with the placebo group (.55), the score in the play and leisure subdomain was significantly greater in the FMT  Abbreviation: FMT, faecal microbiota transplantation.

TA B L E 2
Changes in scores in the FMT and placebo groups from baseline to Week 9 and Week 17, based on the colonisation rate at Week 17.
Data are presented as least-square means with standard errors after adjustment for sex, age and baseline Autism Diagnostic Observation Schedule score.
Overview of adverse events in the FMT and placebo groups.